Chronic kidney disease and end-stage renal disease are major public health problems facing our nation. Understanding the risk factors for progression of chronic renal insufficiency is a crucial but understudied area. The single most important known risk factor for progressive loss of renal function is the amount of proteinuria. However, whether the composition of proteinuria is prognostically important--over and above the quantity of proteinuria--is unknown. This study proposes to apply two-dimensional difference gel electrophoresis (2-D DIGE) to analyze the protein composition of stored urine specimens from subjects enrolled in the ongoing NIDDK-sponsored Chronic Renal Insufficiency Cohort study. We will study 20 subjects with rapid loss of renal function and 20 subjects without, who are matched for major known risk factors for progression. The specific aims of the study are: 1) To perform 2-D DIGE on frozen urine samples from a large ongoing cohort study of chronic renal insufficiency patients;and 2) To compare the pattern of urine protein excretion defined by 2-D DIGE among subjects who have rapid rate of loss of glomerular filtration rate to the pattern among those who do not have rapid loss of glomerular filtration rate. Our goal is to identify proteins that are differentially expressed in the urine of subjects with rapid loss of renal function. This study is in response to NIDDK PAR-06-113 "Pilot And Feasibility Clinical Research Grants In Kidney Or Urologic Diseases (R21)." We believe that this pilot study has the potential to generate exciting preliminary data that will lead to a large-scale study to define more fully how well levels of individual urine protein biomarkers predict loss of glomerular filtration rate. PUBLIC HEALTH RELEVANCE: Our goal is to apply a new technique (2-D DIGE) to analyze the composition of urine protein to better predict which patients with chronic kidney disease will lose kidney function more rapidly. This will help doctors know which patients should be treated more intensely. Discovering new biomarkers will also advance understanding of why certain patients lose kidney function more rapidly and help devise new treatments.